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Intellectual Disability
Intellectual Disability Intellectual Disability '''= significantly sub-average intellectual functioning with related limitations in 2< adaptive skills '''Adaptive Skills = communication; self-care; home living; social skills; leisure; community use; self-direction; health and safety; functional academics; work Formal IQ testing not possible until 5 years of age * Incidence = 1.14% of school age children, 1.8/1000 males, 30% more Males than Females * Identified Cause = 50% Autism Spectrum Disorder/Pervasive Developmental Delay '''= broad spectrum of disease which includes deficiencies in three areas * Social Interaction * Communication * Restrictive, repetitive & stereotypic patterns of behavior, interests, or activities '''Molecular Etiology of Intellectual Disability * 10-12% X-Linked Intellectual Disability * 12% Down Syndrome * 5% Chromosome Structure * >2% Subtelomeric * 15% Pathogenic CNVs * 3% Fragile X * 1.4% 16p13.11 deletion * 1% Inborn Errors of Metabolism * Also: AR, AD Disorders, Environmental Exposures * Unknown X-Linked Intellectual Disability * 153 syndromes, 90+ genes * Syndromic vs. Nonsyndromic (1:2) * Molecular Mechanisms *# Rho/Rab GTPase signaling pathways = involved in neuronal differentiation, synaptic plasticity *# Regulation of gene expression *# Other processes = cell adhesion, transcription regulation, posttranslational modification, signal transduction, ubiquination, actin cytoskeleton modification, sodium transport Intellectual Disability Evaluation * Benefits of Evaluation ** identification of appropriate medical and nonmedical therapies ** identification of indicated medical intervention/referrals ** presymptomatic screening for associated complications/functional disabilities ** educational planning ** elimination of unnecessary testing and evaluations ** anticipatory guidance ** education and advocacy ** referral to appropriate medical/social services ** reproductive counseling, carrier testing, prenatal diagnosis ** family networking * Approach to Evaluation ** Medical History *** prenatal, birth history, birth stats *** neonatal period, hospitalizations *** developmental history = attainment of milestones, progression vs regression *** growth history *** review of systems *** behavior patterns ** Family History *** 3 Generation Pedigree *** Sweep Questions = ID? Learning Disabilities? Psychiatric problems? *** Family Resemblance ** Physical Exam *** growth parameters *** skin findings (with Woods lamp) *** minor anomalies *** measurements *** facial features *** What is the most unusual feature? *** head size - congenital or progressive? ** Neurological Exam *** weakness *** muscle tone *** extrapyramidal signs = hyperreflexia, gait, movements *** cerebellar signs = ataxia *** behavior *** Acute Neurological Changes **** aminoacidopathies **** organic acidurias **** energy production disorders **** lysosomal storage disorders **** peroxisomal disorders *** Loss of skills/Regression/Plateauing **** All of the Above **** Rett Syndrome **** Lesch-Nyhan Syndrome ** Review of Medical Records, Photographs ** Testing *** audiology (always rule out hearing loss) *** ophthalmology *** psychometric assessment *** X-rays *** Neuroimaging **** High frequency of brain abnormalities with ID **** CT best for craniosynostosis, intracranial calcifications **** Useful for: macrocephaly, microcephaly, seizures, loss of psychomotor skills, spasticity *** Metabolic Testing Indications **** FTT **** Recurrent illness **** Seizures **** Ataxia **** Hypotonia **** Coarse Features **** Eye abnormalities **** Recurrent coma/lethargy **** Metabolic Acidosis **** Abnormal Sexual Differentiation **** Hepatosplenomegaly **** Hyperuricemia **** Hyperammonemia **** Low cholesterol **** Structural hair abnormalities **** Unexplained deafness **** Bone abnormalities ***** dysostosis, occipital horns, punctate calcifications **** Skin abnormalities ***** angiokeratoma, ichthyosis ** Test of Time = Diagnoses Increase 5-20% with return visits; phenotypic evolution Syndromes/Conditions Associated With Intellectual Disability * Trisomy 21 = Avg IQ ~50 * Trisomy 18 = Severe * Trisomy 13 * 47, XXX = Mild, IQ ~85-90 * Mosaic Trisomy 8 (Warkany Syndrome) = IQ ~40-75, to normal * Mosaic Trisomy 9 = Severe * Tetrasomy 12p = Profound * Ring X Syndrome * Cat-Eye Syndrome = Borderline * Deletion 4p- (Wolf Hirschhorn Syndrome) = Severe * Deletion 5p- (Cri-du-Chat Syndrome) = Moderate - Severe * WAGR * Williams Syndrome = Mild - Moderate; exceptional verbal ability * Miller-Dieker Syndrome = Profound * Cornelia de Lange Syndrome = IQ <30-100, average 53 * Angelman Syndrome * Coffin-Lowry Syndrome * ARX Gene & Associated Syndromes * Fragile X * Bardet-Biedel * Hypomelanosis of Ito * Smith-Magenis Syndrome * Rett Syndrome * Lesch-Nyhan Syndrome * Homocystinuria * Tuberous Sclerosis * Smith-Lemli-Opitz * Kabuki Syndrome * Menke's Disease